We shall continue to investigate the chemical structure of collagens from cartilage, tendon, skin, bone, and blood vessels, hoping to better understand the function of specific groups on the molecule, particularly those related to crosslinking (lysine, hydroxylysine, derived aldehydes, and condensation products), their number, distribution and rates of synthesis. Human articular cartilage is of importance because of its involvement in the pathogenesis of degenerative joint diseases. Our recent findings indicating that cartilage cells from osteoarthritic areas synthesize a "skin type" collagen shall be further explored. What is the mechanism at the cellular level that underlies this abnormality? How can we reverse such changes? What are the chemical characteristics of the collagen produced in osteoarthritis? We are particularly concerned with the glucosyl-galactosyl-hydroxylysine residues, since they are the most prominent feature of the (alpha 1 - II)3 collagen. What is their exact role? Do they confer a specific ability to certain collagens to interact with the proteoglycans of the connective tissue? It is quite likely that the structural stability of healthy cartilage depends to a great extent on such interactions and that the abnormal collagen deposited in osteoarthritis could lead to a mechanical failure because of a defect. Following our observation that lysosomal enzymes can cause a change in the collagen type synthesized by normal cartilage in organ culture, we want to further explore the mechanism. Osteoarthritis being a focal disease, we want to correlate changes in collagen metabolism with histopathology and lysosmal activity at various sites. We expect that this work will lead to unnerstanding the biochemical defects in osteoarthritis and suggest novel forms of prevention and therapy.